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ACTH-dependent precocious pseudopuberty in an infant with DAX1 gene mutation

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Abstract

DAX1 gene (Xp21) expression is involved in the development of the hypothalamo-pituitary-gonadal and adrenal axes, and acts as a negative regulator of steroidogenesis. Mutations of this gene determine adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism. We report the case of a 9-month-old boy referred for the study of macrogenitosomia and pubic hair development. He had presented acute adrenal crises in the neonatal period and, later, a clinical picture of peripheral precocious puberty. A mutation in the DAX1 gene was found (Trp291Arg) and a diagnosis of AHC was made. Replacement doses of hydrocortisone (HC) (10 mg/m2/day) failed to produce a feedback inhibition of adrenocorticotropic hormone (ACTH), and testosterone levels remained high. Testosterone and ACTH values normalized after HC was progressively increased to 18 mg/m2/day. In conclusion, peripheral precocious puberty in patients with DAX1 gene mutations appears to be secondary to the stimulus exerted by ACTH on melanocortin receptors in Leydig cells and to the overexpression of testicular steroidogenesis activators by the loss of transcriptional repression.

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Acknowledgments

The authors thank Miss Christine O’Hara for her valuable help with the English version of the manuscript. This work has been partially supported by grant RCMN (C03/08) from the Instituto de Salud Carlos III, Madrid, Spain. Guiomar Pérez de Nanclares is an FIS Research Scientist and Gustavo Pérez-Nanclares is an FIS Senior Technician supported by the Spanish Ministry of Health (fellowship nos. CP03/0064 and CA05/0158, respectively). This group is funded, in part, by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, and PI06/0690.

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Authors and Affiliations

  1. Pediatric Endocrinology Department, Hospital Universitario Vall d’Hebron, Autonomous University Barcelona, Paseo Vall d’Hebron, 119–129, 08035, Barcelona, Spain

    Diego Yeste, Cristina González-Niño, Laura Audi & Antonio Carrascosa

  2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain

    Diego Yeste, Laura Audi & Antonio Carrascosa

  3. Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Spain

    Guiomar Pérez de Nanclares, Gustavo Pérez-Nanclares & Luis Castaño

  4. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Barakaldo, Spain

    Guiomar Pérez de Nanclares & Luis Castaño

Authors
  1. Diego Yeste
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  2. Cristina González-Niño
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  3. Guiomar Pérez de Nanclares
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  4. Gustavo Pérez-Nanclares
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  5. Laura Audi
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  6. Luis Castaño
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  7. Antonio Carrascosa
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Correspondence to Diego Yeste.

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Yeste, D., González-Niño, C., Pérez de Nanclares, G. et al. ACTH-dependent precocious pseudopuberty in an infant with DAX1 gene mutation. Eur J Pediatr 168, 65–69 (2009). https://doi.org/10.1007/s00431-008-0710-5

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  • DOI: https://doi.org/10.1007/s00431-008-0710-5

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